CytoSolve Collaborates With World-Renowned Scientists at Leading Universities, Research Institutions and Foundations to Develop and Validate Large-Scale Systems Architecture and Models of Disease and Complex Biological Phenomena.
Pioneering a 23rd Century Research Paradigm
From the systems biology perspective, living organisms can be viewed as being comprised of dynamic networks of biochemical reactions. The origin of disease is characterized by the disruption of one or more signaling cascades, which may arise due to defects at the molecular level. These events ultimately result in the symptomatic manifestation of disease, due to disturbances in usual functions of the cascades involved. Computational modeling of molecular pathways acts as a backbone for the development of disease models. To functionalize computational models as a disease model, one or more signaling molecules function are altered. In complex diseases, there are numerous cells involving different cascades. In such case, an integrative modeling approach assisted by the CytoSolve platform, sheds more light on the effects of the dysfunction mediated by molecular pathways. This could potentially lead to the identification of new biomarkers, targets, and ultimately, therapeutics with beneficial effects in an overall sense rather than those arising from targeting a single molecule. CytoSolve collaborates with leading research institutions in the development of complex and large-scale molecular systems architectures. These architectures are used as a framework in the development of predictive and quantitative models of disease and complex biological phenomena.
Development of Large-Scale Systems Architectures: A Case Study
Zilkha Neurogenetic Institute from University of Southern California (USC) has focussed their research on pericytes to decipher the mysteries of disease mechanisms that impact brain function. Pericytes are perivascular cells that encase around the endothelial cells of capillaries and venules throughout the body. They serve as vital integrators, coordinators and effectors for multiple signals between endothelial cells and astrocytes that are critical for neuronal functions in health and disease. Abnormalities in pericyte function could be an important target for neurodegeneration and psychiatric disorders. USC collaborates with CytoSolve to understand cellular and molecular interaction of pericytes in regulating endothelial cell structure and blood flow. CytoSolve has transformed molecular signaling pathways of PDGF-BB, TGF-β, and Notch into computational model. Scalability of the CytoSolve® Collaboratory™, allows modular integration of molecular pathway models, to analyze the efficient target in blood brain barrier of brain diseases like alzheimer’s disease. Integration and validation of models could be set as an initiative for developing optimized combinations of therapeutic compounds.
Publication in Nature Neuroscience
Development of Large-Scale Molecular Systems Model: A Case Study
Humans were initially considered to possess a different number of genes when compared to a worm. However, during the human genome project, it was realized that humans have the same number of genes as a worm. Biology now recognizes that we cannot consider the human being to be made of just genes, but factors other than genes decides human physiology and disease conditions. These factors could range anything from thoughts, food or lifestyle, giving rise to a thinking based on systems biology. This sheds light on the concept of ‘wholism’, the basis for traditional Indian systems of medicine such as Siddha and Ayurveda. Creating mathematical model of the cell is an effective way of bringing wholism to Western medicine. This involves performing complex integrations of molecular pathway models, generally considered tedious and time-consuming. Various software systems exist for this purpose, however, the approaches used so far do not provide a scalable method to integrate multiple biological pathways to model the whole cell. Dr. VA Shiva Ayyadurai, during his research time at MIT, developed CytoSolve, a scalable architecture for integrating biological pathways. Its key features include an infrastructure that provides simple communications interface to each model, is distributed, Web-enabled, and automatically aggregates the models to build the integrated model. Dr. Shiva Ayyadurai validated CytoSolve by comparing the integrated results of the EGFR pathway with the monolithic model of EGFR generated by CellDesigner, a popular tool for building computational molecular pathway models. The results demonstrated the viability of the CytoSolve approach, which can now provide a basis for using computational methods to solve challenges in medical research.